Diagnosis

Squamous cell carcinoma

Etiology

Cause [4ek]

• UV radiation

• Carcinogens: arsenic, Benzo[a]pyrene, nitrosamines, alkylating chemotherapy

• Chronic inflammation/wound:

  • Human papillomavirus

  • Marjolin ulcer

  • Thermal injury

  • Venous ulcer

  • Lymphedema

  • Discoid lupus erythematosus

  • Lichen planus

  • Lichen sclerosis

  • Keratoderma

  • Necrobiotic lipoidica

• Genetic syndromes:

  Huriez syndrome, xeroderma pigmentosa, oculocutaneous albinism, dyskeratosis congenita, Rothmund-Thomson syndrome, Werner syndrome, Bloom syndrome, dystrophic epidermolysis bullosa, epidermodysplasia verruciformis, Fanconi anemia, keratitis-ichthyosis-deafness syndrome, and genetic immunodeficiency syndromes

Pathophysiology [4ek]

1. Ultraviolet radiation --> chronic inflammation --> increased cell turnover

2. A mutation in the tp53 tumor suppressor gene --> actinic keratosis

3. Decreased immunosurveillance --> Malignant transformation:

   From normal epidermal keratinocytes --> Squamous cell carcinoma

4. Histopathology:

   • Bowen disease: Squamous cell carcinoma in situ

   • Acantholytic/adenoid/pseudoglandular

   • Clear cell

   • Sarcomatoid/spindle cell

   • Desmoplastic

   • Keratoacanthoma

   • Verrucous carcinoma

Risk factors [4ek]

• Age

• Fair skin

• Male gender

• Immunosuppression: Iatrogenic (solid organ transplantation), leukemia, and AIDS

• Medications: BRAF inhibitors, vismodegib, and voriconazole

Complications [4ek]

• Pain

• Loss of function

• Perineural invasion (7%)

• Metastasis (3%)

• Death (1-2%)

Epidemiology

Incidence per 100.000 [85k][sko][qu3][obt][mpo][9bp][msa][w5c][ean]

Approach

• Dermatoscopy

• Biopsy

• CT

• MRI

Staging System [4ek]

• Stage Ti: In situ

• Stage T1: Tumor diameter less than 2 cm

• Stage T2: tumor diameter 2 to 3.9 cm

• Stage T3:

  • Tumor diameter of at least 4 cm

  • Minor bone erosion

  • Perineural invasion at least 0.1 mm or invading a nerve located deeper than the dermis

  • Invasion beyond subcutaneous tissue

  • Invasion greater than 6 mm depth

• Stage T4A: Gross cortical bone or marrow invasion

• Stage T4B: Skull invasion or skull base foramen involvement

Treatment

1. Prophylaxis: Decreasing UVR exposure [6ty][4ek]

2. Low-risk SCC: Electrodessication and curettage

3. Invasive SCC:

   • Surgical excision: Mohs micrographic surgery

   • Radiation therapy adjuvant to surgery

   • Chemotherapy in selected highest-risk cases of SCC

4. Metastatic or locally advanced SCC:

   • Chemotherapy

   • Immunotherapy (programmed death ligand 1 inhibitors)

5. Patients not suitable for surgery:

   • 5-fluorouracil cream

   • Imiquimod cream

   • Cryotherapy

   • Photodynamic therapy

   • Ablative laser

Differential diagnoses

Actinic keratosis, Amyloidosis, Angioma, Atypical fibroxanthoma, Basal cell carcinoma, Benign hereditary intraepithelial dyskeratosis, Burn wound, Eczema, Fibrous xanthoma, Human papillomavirus, Juvenile xanthogranuloma, Kaposi sarcoma, Keratoacanthoma, Leukemia, Lichenoid keratosis, Lichen planus, Lichen sclerosus, Limbal dermoid, Lymphangioma, Lymphoma, Malignant melanoma, Marjolin ulcer, Nevus, Paget's disease, Psoriasis, Pyoderma gangrenosum, Pyogenic granuloma, Rhabdomyosarcoma, Sebaceous cell carcinoma, Seborrheic keratosis, Systemic lupus erythematosus, Verruca vulgaris